Variant rs10923931 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024408.4(NOTCH2):c.875-5592C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152028 control chromosomes in the gnomAD Genomes database, including 2952 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 2952 hom., cov: 32)

Consequence

NOTCH2
NM_024408.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.196

Links

NOTCH2 (HGNC:7882):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOTCH2	NM_024408.4 linkuse as main transcript	c.875-5592C>A		intron_variant		ENST00000256646.7
NOTCH2	NM_001200001.2 linkuse as main transcript	c.875-5592C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
NOTCH2	ENST00000256646.7 linkuse as main transcript	c.875-5592C>A	intron_variant	1	NM_024408.4	P1
NOTCH2	ENST00000479412.2 linkuse as main transcript	n.1013-5592C>A	intron_variant, non_coding_transcript_variant	1
NOTCH2	ENST00000640021.1 linkuse as main transcript	c.94+1014C>A	intron_variant, NMD_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25415

AN:

152028

Hom.:

2952

Cov.:

show subpopulations

Gnomad AFR

AF:

0.325

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0830

Gnomad EAS

AF:

0.0318

Gnomad SAS

AF:

0.190

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.105

Gnomad OTH

AF:

0.156

Alfa

AF:

0.131

Hom.:

644

Bravo

AF:

0.169

Asia WGS

AF:

0.164

AC:

571

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

Cadd

Benign

0.61

Dann

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over